We encapsulated cyclosporine A (CsA) in poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PEG-PLGA) nanoparticles (NPs) by nanoprecipitation of CsA and PEG-PLGA. The resulting CsA/PEG-PLGA-NPs were <100？nm in diameter with a narrow particle size distribution. The NP size could be controlled by tuning the polymer concentration, solvent, or water/solvent ratio during formulation. The PEGylated NPs maintained non-aggregated in salt solution. Solid NPs lyoprotected with bovine serum albumin were prepared for the convenience of storage and transportation. The release kinetics of CsA (55.6% released on Day 1) showed potential for maintaining therapeutic CsA concentrations in vivo. In T-cell assays, both free CsA and CsA/PEG-PLGA-NPs suppressed T-cell proliferation and production of inflammatory cytokines dose dependently. In a mixed lymphocyte reaction assay, the IC50 values for free CsA and CsA/PEG-PLGA-NPs were found to be 30 and 35？ng/mL, respectively. This nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and potentially reduced toxicity. 1. Introduction The efficacy of immunosuppressive drugs has markedly improved over the last 2 decades, and as a result, the 1-year graft survival rate now exceeds 80% for most solid organ transplant. However, only modest improvements of long-term graft survival rates have been achieved, owing mainly to the systemic toxicity of immunosuppressants. When calcineurin inhibitors were introduced in mid-1980s, they revolutionized the field of transplantation by substantially reducing the rate of acute rejection [1, 2]. In particular, the discovery of cyclosporine A (CsA), a highly lipophilic neutral cyclic peptide, was a milestone in organ transplantation and the treatment of autoimmune diseases. CsA effectively suppresses immune reactions dependency on T cells, which are the key effector cells involved in graft rejection and autoimmunity. It forms a complex with cyclophilin, a cytoplasmic receptor protein present in T lymphocytes, and this complex then binds to calcineurin and inhibits Ca2+-stimulated dephosphorylation of the cytoplasmic component of the nuclear factor of activated T cells. This factor regulates transcription of numerous genes involved in T-cell activation and proliferation, such as IL-2, IL-4, and CD40 ligand [14]. When these genes are not expressed, T-cell-dependent immune responses are dramatically inhibited. However, CsA exhibits low oral bioavailability owing to its poor biopharmaceutical properties,
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